CHMP Backs EU Approval of Belzutifan Plus Lenvatinib for ccRCC
The European Medicines Agency's human medicines committee has backed belzutifan plus lenvatinib for adults with advanced clear cell kidney cancer after a PD-1 or PD-L1 inhibitor. Merck said the European Commission is expected to decide within two months. The recommendation rests on the phase 3 LITESPARK-011 trial of 747 patients.
The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending approval of belzutifan (Welireg) plus lenvatinib (Lenvima) for adults with advanced renal cell carcinoma with a clear cell component (ccRCC) after a PD-1 or PD-L1 inhibitor, Urology Times reported, citing Merck. The CHMP recommends EU approval of the combination for advanced ccRCC in patients whose disease has progressed after that earlier immunotherapy.
The European Commission will now review the recommendation. Merck expects a decision within the next two months.
If granted, marketing authorization would apply to all 27 European Union member states, plus Iceland, Liechtenstein and Norway. The combination was approved in the United States for advanced ccRCC in September 2026.
The recommendation rests on the phase 3 LITESPARK-011 trial, which enrolled 747 patients. Participants had locally advanced or metastatic ccRCC that progressed on or after a PD-1 or PD-L1 inhibitor, or within six months of finishing adjuvant therapy with a PD-1 inhibitor.
Patients received either 120 mg of belzutifan with 20 mg of lenvatinib, both taken orally once daily, or 60 mg of cabozantinib (Cabometyx) once daily.
The combination cut the risk of disease progression or death by 26% compared with cabozantinib (HR, 0.74; 95% CI, 0.61 to 0.89; P = .001). Median progression-free survival was 14.8 months with the combination and 10.8 months with cabozantinib.
The secondary end point of overall survival missed statistical significance. Median overall survival was 33.7 months with the combination versus 28.6 months with cabozantinib (HR, 0.85).
Response rates improved. The objective response rate was 53.1% versus 40.2%, and the complete response rate was 6.7% versus 1.3%.
The side effect profiles differed. Anemia and hypoxia were higher with the combination, while diarrhea, hand-foot syndrome (PPE) and stomatitis were more common with cabozantinib. Grade 3 or higher adverse events were similar between the arms. Serious adverse events and treatment-emergent deaths were more frequent with the combination.
Cardiac dysfunction occurred in 13.0% of patients on belzutifan plus lenvatinib versus 8.1% on cabozantinib. Hypertension was common in both arms.
The results were first presented at the 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. Final overall survival data were presented at the 2026 European Society for Medical Oncology Congress in Madrid and published in Annals of Oncology.
"Patients with advanced renal cell carcinoma in the European Union have limited treatment options if their disease progresses following anti-PD-1 or anti-PD-L1 therapy," said Dr. Christina Derleth, vice president, global oncology clinical development, Merck Research Laboratories. She called the opinion "a meaningful step toward potentially bringing this first-of-its-kind regimen to patients in need in the European Union."
